Our long-term goal is to understand the pathogenesis of bacterial otitis media and to develop a multivalent vaccine that reduces the incidence of otitis media caused by all major bacterial pathogens in children. Lipooligosaccharide (LOS), a major bacterial surface component of Moraxella catarrhalis, is a possible virulence factor in the pathogenesis of human infections caused by the organism. In the passing year, we have identified a kdtA gene, which is responsible for adding sugar (Kdo) residues to the lipid A portion of the LOS. Studies showed that the oligosaccharide moiety of the LOS is important for the biological activity of the LOS and the virulence capability of the bacteria. This study may bring new insights into novel vaccines or therapeutic interventions against M. catarrhalis infections. In addition, we have used the bacterial surface antigen, LOS, as a component to develop new conjugate vaccines against serotype B M. catarrhalis. Previous studies suggest that only three serotypes (A, B, and C) have been identified among clinical isolates. Our previous laborotory results revealed that serotype A LOS-based conjugate vaccines were safe and effective in animal models. Our current testing in animal experiments with the newly developed serotype B vaccines for M. catarrhalis demonstrated that the vaccines were safe and effective to elicit an immune response that inhibited bacterial growth. These studies are significant advances towards future clinical trials to test these candidate vaccines for safety and efficacy in humans.